Inactive extra-chromosomal MYCN amplicons co-localize to the nuclear lamina in therapy-induced senescent neuroblastoma cells

Introduction: Neuroblastoma (NB) is the most common solid tumour in childhood. MYCN amplification, frequently extrachromosomally, is associated with aggressive tumour behaviour. Metronomic topotecan (TPT) and other drugs can induce cellular senescence, a stable cell cycle arrest, in NB in vitro and in vivo leading to a reduction of MYCN gene copies and abrogation of MYCN expression, however the underlying mechanisms are poorly understood. Methods: Co-localisation analysis of MYCN FISH and lamin immunofluorescence stainings; Lamin A/C knock-down with subsequent Western Blot analysis of MYCN and p21WAF1/CIP1 and F…